Urinary Exosomal Tissue TIMP and Angiopoietin-1 Are Preoperative Novel Biomarkers of Well-Differentiated Thyroid Cancer

Abstract

Finding non-invasive and sensitive biomarkers for early screening of high-risk patients remains important in clinical practice. A higher concentration of urine exosomal thyroglobulin protein was found in late-stage patients with thyroid carcinoma compared to those with early stage in our previous study. This prospective study aims to find new prognostic biomarkers before surgery for decision-making with this platform. We enrolled patients newly diagnosed with papillary and follicular cancer from 2017 to 2018. Preoperative urine samples were collected and the exosomal proteins were analyzed. The association of the concentration of urine exosomal proteins with lymph node metastasis and MACIS score (metastasis, age, completeness of resection, invasion, and size) was analyzed with multiple logistic regression. In total, 21 patients were included, with a mean age of 51.29 ± 10.29 years and a majority of female patients (85.71%). The concentration of urine exosomal TIMP (tissue inhibitor of metalloproteinase) was significantly higher in patients with lymph node metastasis (p = 0.01). Multiple logistic regression analysis showed association of urine exosomal TIMP (adjusted odds ratio (aOR): 3.09, 95% confidence interval (CI): 0.99–9.6, p = 0.052), angiopoietin-1 (aOR: 2.24, 95% CI: 0.97–5.15, p = 0.058) with lymph node metastasis. However, no association was noted between MACIS score and various urine exosomal protein candidates. Preoperative urine exosomal data could suggest certain peptides having the potential as prognostic indicators for screening patients with high-risk before surgery. Further study with a large cohort and long follow-up is needed to identify the application of urine exosomal proteins on prognostic prediction.

Keywords

• thyroid cancer
• exosome
• urine
• angiopoietin-1
• TIMP (tissue inhibitor of metalloproteinase)